The goal of this proposal is to identify sensory- and motor-driven genes activated by learned vocal communication in normal and deafened subjects. The animal model we will utilize is a songbird. Songbirds are one of the only accessible non-human animals where learned vocal communication, the substrate for human language, can be studied. Non-human primates, rodents, and other commonly studied animals do not have; this ability. In songbirds, hearing species-specific vocalizations (sensory activity) induces large increases of gene expression throughout the auditory pathway. This sensory-driven expression is experience-dependent, as induction requires that the birds be raised with adult conspecifics and induction is highest when the birds hear novel species-specific songs. The expression is blocked by deafening. The act of producing imitated vocalizations (motor activity) induces large increases of gene expression throughout the cerebral vocal pathway, and this motor-driven expression is not blocked by deafening. However, when birds are deafened, like humans, their learned vocalizations deteriorate. This deterioration, in songbirds, is an active process that requires the basal ganglia cortical-like vocal pathway, in which vocalizing-driven gene expression is found. To date, few genes have been identified with such sensory- and motor-driven regulation during behavior and none have yet been identified that change with deafening-induced deterioration of learned vocalizations. It is believed that an entire gene regulatory network is activated in these behavioral processes. We will use behavioral, neuroanatomical, and high throughput molecular biological approaches to identify and characterize sensory and motor-driven genes activated by normal vocal communication and by deafened-induced deterioration of learned vocalizations. Since most songbird genes have significant homology to known mammalian genes our experiments will enable us to identify avian brain genes with humain/mammalian homologues amenable to experimental characterization in the songbird system.